PICALM::MLLT10 may indicate a new subgroup of acute leukemias with miscellaneous immunophenotype and poor initial treatment response but showing sensitivity to venetoclax.

The PICALM::MLLT10 fusion gene is a rare but recurrent event in acute leukemia (AL) associated with poor prognosis. It is still confused whether PICALM::MLLT10 can solely correspond to acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or acute leukemias of ambiguous lineage (ALAL). Here, we reported a series of PICALM::MLLT10 positive AL patients with miscellaneous immunophenotype including T-ALL, ALAL, AML, and B-ALL, complex karyotype, half of extramedullary disease (EMD), frequently concomitant PHF6 mutation, and poor initial treatment response to standard chemotherapy aiming to different immunophenotype, but showing sensitivity to combining chemotherapy especially integrated with venetoclax, suggesting this fusion gene may indicate a new subgroup of AL. Eighteen PICALM::MLLT10 positive patients of 533 AL patients (18/533, 3.4%) were identified by RNA sequencing in our center. We found PICALM::MLLT10 positive AL showing miscellaneous immunophenotype, higher expression of leukemic stemness genes and lower expression of biomarkers of venetoclax resistance, more extramedullary involvement, and especially poor response to conventional induction chemotherapy, but may benefit from venetoclax as well as low-dose Ara-C, granulocyte colony-stimulating factor (G-CSF), and anthracyclines combination chemotherapy. Sequential hematopoietic stem cell transplantation (HSCT) after chemotherapy combined with venetoclax may further improve long-term survival in AL patients with complete remission (CR) even measurable residual disease (MRD) positive.

Enhanced chlorobenzene removal by internal magnetic field through initial cell adhesion and biofilm formation.

Magnetic fields (MF) have been proven efficient in bioaugmentation, and the internal MFs have become competitive because they require no configuration, despite their application in waste gas treatment remaining largely unexplored. In this study, we firstly developed an intensity-regulable bioaugmentation with internal MF for gaseous chlorobenzene (CB) treatment with modified packing in batch bioreactors, and the elimination capacity increased by up to 26%, surpassing that of the external MF. Additionally, the microbial affinity to CB and the packing surface was enhanced, which was correlated with the ninefold increased secreted ratio of proteins/polysaccharides, 43% promoted cell surface hydrophobicity, and half reduced zeta potential. Furthermore, the dehydrogenase content was promoted over 3 times, and CB removal steadily increased with the rising intensity indicating enhanced biofilm activity and reduced CB bioimpedance; this was further supported by kinetic analysis, which resulted in improved cell adhesive ability and biological utilisation of CB. The results introduced a novel concept of adjustable magnetic bioaugmentation and provided technical support for industrial waste gas treatments. KEY POINTS: • Regulable magnetic bioaugmentation was developed to promote 26% chlorobenzene removal • Chlorobenzene mineralisation was enhanced under the magnetic field • Microbial adhesion was promoted through weakening repulsive forces.

Enhancement of gaseous chlorobenzene biodegradation and power generation in a microbial fuel cell by bifunctional Acinetobacter sp. HY-99C.

The efficient biodegradation of volatile chlorinated hydrocarbons using microbial fuel cells (MFCs) offers a feasible approach for purifying waste gas and alleviating energy crises. However, power generation is limited by poor pollutant biodegradation and slow electron transfer. The bifunctional bacterium Acinetobacter sp. HY-99C was screened and used to improve the performance of a conventional MFC. The inoculation of strain HY-99C into the conventional MFC promoted the formation of a compact biofilm with high metabolic activity and an enriched bifunctional genus (Acinetobacter), which resulted in the accelerated decomposition of chlorinated aromatic compounds into biodegradable organic acids. This led to efficient chlorobenzene removal and power generation from the MFC, with a chlorobenzene elimination capacity of 70.8 g m-3 h-1 and power density of 89.6 mW m-2, which are improved over those of previously reported MFCs. This study provides novel insights into enhancing pollutant removal and power generation in MFCs.

Three atypical BCR/ABL transcripts detected simultaneously in a Philadelphia-positive acute lymphoblastic leukemia patient showing resistance to tyrosine kinase inhibitors.

The Philadelphia (Ph) chromosome with a BCR/ABL fusion gene is a characteristic feature of chronic myeloid leukemia (CML) and partial acute lymphoblastic leukemia (ALL) patients, with different breakpoints of the BCR and ABL genes. Here, we report the case of a Ph-positive ALL patient with poor prognosis in whom simultaneous different BCR/ABL transcripts named e1a3, e1a4, and e1a5 were detected by RNA-seq analysis but not traditional RT-PCR. To our knowledge, this is the first report to describe coexistence of different atypical BCR-ABL transcripts in the same patient and that traditional TKI therapy may not overcome the poor prognosis. This finding will bring new challenges in diagnosis and monitoring for minimal residual disease.

Bone marrow infiltrated natural killer cells predicted the anti-leukemia activity of MCL1 or BCL2 inhibitors in acute myeloid leukemia.

Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.

Outcomes of Endonasal Septoplasty and Extracorporeal Septal Reconstruction in Anterocaudal Septal Deviation.

OBJECTIVE: The aim of this study was to compare the functional and aesthetic outcomes of endonasal septoplasty (ES) and extracorporeal septal reconstruction (ESR) in anterocaudal septal deviation. METHODS: In this study, patients (n = 46) who underwent nasal septoplasty surgery due to anterocaudal septal deviation during February 2015 to August 2017 were analyzed; 23 patients underwent ES and the others (n = 23) underwent ESR. The decision of whether to use the ES or ESR was randomized by random number table method. Nasal obstruction symptoms evaluation (NOSE) scores, total nasal resistance (TNR), aesthetic visual analog scale (VAS), nasal anatomical angles, and incidence of complications were used to assess the patients in 2 groups. RESULTS: The NOSE scores, TNR, aesthetic VAS, tip deviation angle (TDA), nasolabial angle (NLA), nasofrontal angle (NFA) in the ESR group were significantly improved from preoperative to postoperative 1 year, whereas in the ES group, except aesthetic VAS, NLA, NFA, all other postoperative outcomes were improved from preoperative values. The objective and subjective postoperative results of ESR group were better than the ES group except TDA. The incidence of complications was not significantly different between the 2 groups. CONCLUSION: Our study have compared the nasal functional and aesthetic outcomes of 2 septoplasty techniques in a randomized controlled trial. The ESR technique is more effective than ES technique in correcting functional and aesthetic disorders caused by anterocaudal septal deviation.

MiR-103 regulates the angiogenesis of ischemic stroke rats by targeting vascular endothelial growth factor (VEGF).

OBJECTIVES: To investigate the effect of miR-103 on the angiogenesis of ischemic stroke rats via targeting vascular endothelial growth factor (VEGF) at the molecular level. MATERIALS AND METHODS: Rat models had received the middle cerebral artery occlusion (MCAO) or sham operation before grouping, and cell models of oxygen-glucose deprivation (OGD) were performed. FITC-dextran, matrigel, and Trans-well assays were used to evaluate the vascular density, tube formation, and cell migration respectively. The expression levels of miR-103 and VEGF were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Dual-luciferase assay was used for analyzing the targeting relationship between miR-103 and VEGF. RESULTS: We found the reduced miR-103 in rats after MCAO. Down-regulating miR-103 with the miR-103 inhibitor enhanced VEGF, ameliorated the neurological scores, decreased infarct volume, and increased vascular density in rats after MCAO. Besides, in OGD human umbilical vein endothelial cells (HUVECs), inhibition of miR-103 could promote the increase of tube length and the migration of cells. Additionally, we found that miR-103 could directly target VEGF and thereby lead to the down-expression of VEGF. Meanwhile, si-VEGF could reverse the effect of miR-103 inhibitor on angiogenesis in rats subjected to MCAO. CONCLUSION: Inhibition of miR-103 could promote ischemic stroke angiogenesis and reduce infarction volume via enhancing VEGF, which provides a new target for the clinical treatment of ischemic stroke.

PALLD Regulates Phagocytosis by Enabling Timely Actin Polymerization and Depolymerization.

PALLD is an actin cross-linker supporting cellular mechanical tension. However, its involvement in the regulation of phagocytosis, a cellular activity essential for innate immunity and physiological tissue turnover, is unclear. We report that PALLD is highly induced along with all-trans-retinoic acid-induced maturation of myeloid leukemia cells, to promote Ig- or complement-opsonized phagocytosis. PALLD mechanistically facilitates phagocytic receptor clustering by regulating actin polymerization and c-Src dynamic activation during particle binding and early phagosome formation. PALLD is also required at the nascent phagosome to recruit phosphatase oculocerebrorenal syndrome of Lowe, which regulates phosphatidylinositol-4,5-bisphosphate hydrolysis and actin depolymerization to complete phagosome closure. Collectively, our results show a new function for PALLD as a crucial regulator of the early phase of phagocytosis by elaborating dynamic actin polymerization and depolymerization.

[Analysis of CEBPA mutation in acute myeloid leukemia].

In order to evaluate the incidence of CCAAT/enhancer binding protein alpha (cebpa) gene mutation in patients with acute myeloid leukemia (AML), 22 AML patients with normal karyotype (NK-AML) were enrolled in this study, including de novo AML and relapsed AML. The cebpa gene was amplified by 2 stages using genomic DNA as template, the cebpa gene mutation amplified product was detected by direct sequencing or clone sequencing. The results showed that the cebpa mutations including deletion and insertion were found in 4 out of 22 AML patients (18.2%) and all of these 4 patients were M(2). Two patients had N-terminal nonsense mutation and the other two had C-terminal in-frame mutation. It is concluded that PCR combined with direct sequencing and clone sequencing can be used to detect cebpa mutations. cebpa mutations are mainly identified in M(2) subtype of NK-AML patients, its significance for prognosis needs to further investigate.

[Immunophenotypic features in 143 cases of acute promyelocytic leukemia].

This study was aimed to investigate the immunophenotypic characteristics of acute promyelocytic leukemia (APL). CD45/Side Scatter (SSC) gating strategy and multiparametric flow cytometry were used to determine immunophenotype of 143 patients with APL. The immunophenotypic features were compared between newly diagnosed APL patients and relapsed APL patients. 42 patients with HLA-DR(-) (non-APL AML, DR(-)AML) were randomly selected as controls. 31 out of 42 AML patients were CD34 negative, and their immunophenotypes were compared with those in newly diagnosed APL patients. The results showed that (1) CD34 and HLA-DR were both negative in 91.9% of newly diagnosed APL, while the positive rate of CD34 and HLA-DR elevated in relapsed cases (3.0% vs 37.5%, 3.9% vs 37.5%). The positive rate of CD34 in HLA-DR(-) AML group was higher than that in newly diagnosed APL group (23.4% vs 3.0%). The positive level of CD34 in newly diagnosed APL group was lower than that in HLA-DR(-) AML group; (2) the positive rate of CD33 in newly diagnosed APL group was higher than that in other groups (97.0% vs 75.0%, 83.3%, 83.9%), as well as the the positive level of CD33 (p < 0.05). (3) no lymphoid antigen other than CD2 was expressed in newly diagnosed APL group. The positive rate of CD7 was 9.5% in DR(-) AML group and 6.5% in CD34(-)/DR(-) AML group, both were higher than those of newly diagnosed APL group (p < 0.05). It is concluded that the immunophenotyping can provide proof to the rapid diagnosis of APL. For those patients with DR(-) AML, it may be helpful to identify APL depending on following features: low or negative CD34 expression, homogeneous and bright expression of CD33, no lymphoid antigens other than CD2, higher SSC.